The etiologic agent of AIDS is the human immunodeficiency virus (HIV) which differs from most other human viral diseases in exhibiting a very prolonged latent period, but ultimately being lethal due to a profound effect on the immune system. Several trans-acting HIV genes appear to be crucial to HIV growth and infection. Therefore we are studying the feasibility of a novel anti-viral therapy for HIV based on interference by another viral gene with the trans-acting regulation of HIV. The overall goal of this proposal is to analyze interactions between trans-acting regulatory genes of HIV and of a human parvovirus, adeno-associated virus, AAV. We are analyzing the AAV rep gene and its interaction with the HIV tat gene. Current work suggests that developing standard types of anti- viral therapy such as vaccines or nucleotide-analog drugs for HIV is difficult and other alternate possibilities for therapy must be investigated. One approach is to intervene in the trans-regulation system of HIV especially that mediated by the HIV tat gene. Thus a possible anti-viral therapy for HIV is to inhibit the production or the action of tat. A novel way to attempt this is to employ a trans-acting gene from another human virus. One such candidate is the rep gene of the human parvovirus adeno-associated virus (AAV). AAV does not cause any human disease and grows only in cells also infected with adenovirus or herpes viruses. AAV inhibits growth of the helper virus and may play an important role in limiting certain human viral infections. Also AAV can alter important regulatory controls in virus infected cells or in tumor cells. Rep is a novel type of trans-acting regulatory gene which exhibits negative, translational regulation of many genes in several cell types. We are analyzing the AAV rep gene and its interaction with the HIV tat gene. We are testing rep as a potential trans-acting heterologous inhibitor of HIV.